1213P DKN-01 and tislelizumab + chemotherapy as first-line (1L) investigational therapy in advanced gastroesophageal adenocarcinoma (GEA): DisTinGuish trial

Despite recent approval of anti-PD-1 antibodies as 1L therapy in advanced GEA, benefit is largely limited to PD-L1 combined positive scores (CPS) ≥5 patients (pts); novel therapeutic approaches are needed. DKN-01 a targeted anti-DKK1 mAb which has demonstrated activity GEA pts with elevated tumoral DKK1 expression, subset more aggressive disease and shorter overall survival. Phase IIa single arm trial investigating 300 mg (D) + tislelizumab (TS) CAPOX HER2(-) regardless status. Tumoral mRNA expression was assessed by chromogenic situ hybridization RNAscope assay assigned an H-score (0-300). Primary endpoint ORR modified intent treat (mITT) population (>1 dose D); secondary endpoints included PFS OS (ITT) expression: high (H-score ≥35) vs low. 25 enrolled (01 Sept 2020 - 08 Apr 2021). Median age 61 years (22, 80); 17 gastroesophageal junction adenocarcinoma; 8 gastric cancer. 21 had expression; 57% were DKK1-high. 22 vCPS: 73% vCPS <5. duration treatment 11.3 mos. 7 on only 9 have died. 12 mo survival: 76%. 14 (56%) experienced D-TRAEs (treatment related adverse events), most (96%) G1/2. Most common regimen TRAEs nausea (72%), fatigue (64%), diarrhoea (56%). 5 ≥G3 D-TRAEs: hypophosphatemia (2), pulmonary embolism (2, one G5), neutropenia (1), (1).Table: 1213PORR mITT*, n=22 (n,%)Median DoR, mos (n=15)*Median PFS, mos, ITT (n=25)CRPRSDNEOverall15 (68)1 (5)14 (64)6 (27)1 (5)10.011.3DKK1 high, n=109 (90)-9 (90)-1 (10)10.611.6DKK1 low, n=95 (56)1 (11)4 (44)4 (44)-10.612.0DKK1 unk, n=31 (33)-1(33)2 (67)-7.08.4*4 responders ongoing (2 2 low) Open table new tab *4 D/TS well-tolerated, active combination, including DKK1-high CPS low patients, subpopulations GEA. With 36% deceased the data cut, not mature. Further study plus standard care IL warranted.